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6 pages, 205 KiB

Open AccessEditorial

Bioactives and Inflammation

by Guan-Ting Liu and Chan-Yen Kuo

Curr. Issues Mol. Biol. 2023, 45(7), 5824-5829; https://doi.org/10.3390/cimb45070368 - 13 Jul 2023

Cited by 1 | Viewed by 1273

Abstract

Inflammation is one of the body’s most complex physiological defense mechanisms against harmful substances [...] Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

Research

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18 pages, 12742 KiB

Open AccessArticle

Whole Transcriptome Analysis of Intervention Effect of Sophora subprostrate Polysaccharide on Inflammation in PCV2 Infected Murine Splenic Lymphocytes

by Yi Zhao, Nina Jia, Xiaodong Xie, Qi Chen and Tingjun Hu

Curr. Issues Mol. Biol. 2023, 45(7), 6067-6084; https://doi.org/10.3390/cimb45070383 - 20 Jul 2023

Cited by 2 | Viewed by 1632

Abstract

(1) Background: Sophora subprostrate, is the dried root and rhizome of Sophora tonkinensis Gagnep. Sophora subprostrate polysaccharide (SSP1) was extracted from Sophora subprostrate, which has shown good anti-inflammatory and antioxidant effects. Previous studies showed SSP1 could modulate inflammatory damage induced by [...] Read more.

(1) Background: Sophora subprostrate, is the dried root and rhizome of Sophora tonkinensis Gagnep. Sophora subprostrate polysaccharide (SSP1) was extracted from Sophora subprostrate, which has shown good anti-inflammatory and antioxidant effects. Previous studies showed SSP1 could modulate inflammatory damage induced by porcine circovirus type 2 (PCV2) in murine splenic lymphocytes, but the specific regulatory mechanism is unclear. (2) Methods: Whole transcriptome analysis was used to characterize the differentially expressed mRNA, lncRNA, and miRNA in PCV2-infected cells and SSP1-treated infected cells. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and other analyses were used to screen for key inflammation-related differentially expressed genes. The sequencing results were verified by RT-qPCR, and western blot was used to verify the key protein in main enriched signal pathways. (3) Results: SSP1 can regulate inflammation-related gene changes induced by PCV2, and its interventional mechanism is mainly involved in the key differential miRNA including miR-7032-y, miR-328-y, and miR-484-z. These inflammation-related genes were mainly enriched in the TNF signal pathway and NF-κB signal pathway, and SSP1 could significantly inhibit the protein expression levels of p-IκB, p-p65, TNF-α, IRF1, GBP2 and p-SAMHD1 to alleviate inflammatory damage. (4) Conclusions: The mechanism of SSP1 regulating PCV2-induced murine splenic lymphocyte inflammation was explored from a whole transcriptome perspective, which provides a theoretical basis for the practical application of SSP1. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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16 pages, 3676 KiB

Open AccessArticle

Magnolia kobus Extract Suppresses Porphyromonas gingivalis LPS-Induced Proinflammatory Cytokine and MMP Expression in HGF-1 Cells and Regulates Osteoclastogenesis in RANKL-Stimulated RAW264.7 Cells

by Hae Jin Lee, So Jung Lee, Sung Kwon Lee, Bong Keun Choi, Dong Ryung Lee, Ju-Hyoung Park and Joa Sub Oh

Curr. Issues Mol. Biol. 2023, 45(6), 4875-4890; https://doi.org/10.3390/cimb45060310 - 3 Jun 2023

Viewed by 2043

Abstract

Clinical prevention is of utmost importance for the management of periodontal diseases. Periodontal disease starts with an inflammatory response in the gingival tissue, and results in alveolar bone destruction and subsequent tooth loss. This study aimed to confirm the anti-periodontitis effects of MKE. [...] Read more.

Clinical prevention is of utmost importance for the management of periodontal diseases. Periodontal disease starts with an inflammatory response in the gingival tissue, and results in alveolar bone destruction and subsequent tooth loss. This study aimed to confirm the anti-periodontitis effects of MKE. To confirm this, we studied its mechanism of action using qPCR and WB in LPS-treated HGF-1 cells and RANKL-induced osteoclasts. We found that MKE suppressed proinflammatory cytokine protein expression by inhibiting the TLR4/NF-κB pathway in LPS-PG-induced HGF-1 cells and blocking ECM degradation by regulating the expression of TIMPs and MMPs. We also confirmed that TRAP activity and multinucleated cell formation were reduced in RANKL-stimulated osteoclasts after exposure to MKE. These results were confirmed by inhibiting TRAF6/MAPK expression, which led to the suppression of NFATc1, CTSK, TRAP, and MMP expression at the gene and protein levels. Our results confirmed that MKE is a promising candidate for the management of periodontal disease based on its anti-inflammatory effects and inhibition of ECM degradation and osteoclastogenesis. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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20 pages, 5677 KiB

Open AccessArticle

Anti-Inflammatory and Anti-Quorum Sensing Effect of Camellia sinensis Callus Lysate for Treatment of Acne

by Mariona Cañellas-Santos, Elisabet Rosell-Vives, Laia Montell, Ainhoa Bilbao, Felipe Goñi-de-Cerio and Francisco Fernandez-Campos

Curr. Issues Mol. Biol. 2023, 45(5), 3997-4016; https://doi.org/10.3390/cimb45050255 - 4 May 2023

Cited by 7 | Viewed by 2860

Abstract

Cutibacterium acnes (C. acnes) is involved in the pathogenesis of acne by inducing inflammation and biofilm formation, along with other virulence factors. A Camellia sinensis (C. sinensis) callus lysate is proposed to reduce these effects. The aim of the [...] Read more.

Cutibacterium acnes (C. acnes) is involved in the pathogenesis of acne by inducing inflammation and biofilm formation, along with other virulence factors. A Camellia sinensis (C. sinensis) callus lysate is proposed to reduce these effects. The aim of the present work is to study the anti-inflammatory properties of a callus extract from C. sinensis on C. acnes-stimulated human keratinocytes and the quorum-quenching activities. Keratinocytes were stimulated with thermo-inactivated pathogenic C. acnes and were treated with the herbal lysate (0.25% w/w) to evaluate its anti-inflammatory effect. C. acnes biofilm was developed in vitro and treated with 2.5 and 5% w/w of the lysate to evaluate quorum sensing and the lipase activity. The results showed that the lysate was able to reduce the production of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and C-X-C motif chemokine ligand 1 (CXCL1), and decrease the nuclear translocation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB). The lysate did not show bactericidal activity but showed diminished biofilm formation, the lipase activity, and the production of autoinducer 2 (AI-2), a member of a family of signaling molecules used in quorum sensing. Therefore, the proposed callus lysate could have the potential to reduce acne-related symptoms without the eradication of C. acnes, which is part of the natural skin microbiome. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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12 pages, 2612 KiB

Open AccessArticle

Serratiopeptidase Attenuates Lipopolysaccharide-Induced Vascular Inflammation by Inhibiting the Expression of Monocyte Chemoattractant Protein-1

by Vikas Yadav, Satyam Sharma, Ashutosh Kumar, Sanjiv Singh and V. Ravichandiran

Curr. Issues Mol. Biol. 2023, 45(3), 2201-2212; https://doi.org/10.3390/cimb45030142 - 8 Mar 2023

Cited by 5 | Viewed by 3822

Abstract

Lipopolysaccharide (LPS) has potent pro-inflammatory properties and acts on many cell types including vascular endothelial cells. The secretion of the cytokines MCP-1 (CCL2), interleukins, and the elevation of oxidative stress by LPS-activated vascular endothelial cells contribute substantially to the pathogenesis of vascular inflammation. [...] Read more.

Lipopolysaccharide (LPS) has potent pro-inflammatory properties and acts on many cell types including vascular endothelial cells. The secretion of the cytokines MCP-1 (CCL2), interleukins, and the elevation of oxidative stress by LPS-activated vascular endothelial cells contribute substantially to the pathogenesis of vascular inflammation. However, the mechanism involving LPS-induced MCP-1, interleukins, and oxidative stress together is not well demonstrated. Serratiopeptidase (SRP) has been widely used for its anti-inflammatory effects. In this research study, our intention is to establish a potential drug candidate for vascular inflammation in cardiovascular disorder conditions. We used BALB/c mice because this is the most successful model of vascular inflammation, suggested and validated by previous research findings. Our present investigation examined the involvement of SRP in vascular inflammation caused by lipopolysaccharides (LPSs) in a BALB/c mice model. We analyzed the inflammation and changes in the aorta by H&E staining. SOD, MDA, and GPx levels were determined as per the instructions of the kit protocols. ELISA was used to measure the levels of interleukins, whereas immunohistochemistry was carried out for the evaluation of MCP-1 expression. SRP treatment significantly suppressed vascular inflammation in BALB/c mice. Mechanistic studies demonstrated that SRP significantly inhibited the LPS-induced production of proinflammatory cytokines such as IL-2, IL-1, IL-6, and TNF-α in aortic tissue. Furthermore, it also inhibited LPS-induced oxidative stress in the aortas of mice, whereas the expression and activity of monocyte chemoattractant protein-1 (MCP-1) decreased after SRP treatment. In conclusion, SRP has the ability to reduce LPS-induced vascular inflammation and damage by modulating MCP-1. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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15 pages, 3820 KiB

Open AccessArticle

Crocin Attenuates NLRP3 Inflammasome Activation by Inhibiting Mitochondrial Reactive Oxygen Species and Ameliorates Monosodium Urate-Induced Mouse Peritonitis

by Ruth Sangare, Iskander Madhi, Ji-Hee Kim and YoungHee Kim

Curr. Issues Mol. Biol. 2023, 45(3), 2090-2104; https://doi.org/10.3390/cimb45030134 - 3 Mar 2023

Cited by 5 | Viewed by 1969

Abstract

Crocin is a hydrophilic carotenoid pigment found in the stigma of Crocus sativus or the fruit of Gardenia jasminoides. In this study, we investigated the effects of Crocin on the activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing [...] Read more.

Crocin is a hydrophilic carotenoid pigment found in the stigma of Crocus sativus or the fruit of Gardenia jasminoides. In this study, we investigated the effects of Crocin on the activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3) inflammasome in J774A.1 murine macrophage cells and monosodium urate (MSU)-induced peritonitis. Crocin significantly inhibited Nigericin-, adenosine triphosphate (ATP)-, MSU-induced interleukin (IL)-1β secretion, and caspase-1 cleavage without affecting pro-IL-1β and pro-caspase-1. Crocin also suppressed gasdermin-D cleavage and lactate dehydrogenase release and enhanced cell viability, indicating that Crocin reduces pyroptosis. Similar effects were observed in primary mouse macrophages. However, Crocin did not affect poly(dA:dT)-induced absent in melanoma 2 (AIM2) and muramyl dipeptide-induced NLRP1 inflammasomes. Crocin decreased Nigericin-induced oligimerization and the speck formation of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). Crocin also dramatically alleviated the ATP-induced production of mitochondrial reactive oxygen species (mtROS). Finally, Crocin ameliorated the MSU-induced production of IL-1β and IL-18 and the recruitment of neutrophils during peritoneal inflammation. These results suggest that Crocin suppresses NLRP3 inflammasome activation by blocking mtROS production and ameliorates MSU-induced mouse peritonitis. Thus, Crocin may have therapeutic potential in various NLRP3 inflammasome-related inflammatory diseases. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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17 pages, 4930 KiB

Open AccessArticle

Therapeutic Effects of Aloe saponaria against Ulcerative Colitis Induced by Dextran Sulfate Sodium

by Do Yeong Kweon, Hee Jin Song, Ji Eun Kim, You Jeong Jin, Yu Jeong Roh, Ayun Seol, Ju Min Park, Eun Suk Lee, Won Sik Choi and Dae Youn Hwang

Curr. Issues Mol. Biol. 2023, 45(2), 1483-1499; https://doi.org/10.3390/cimb45020096 - 9 Feb 2023

Cited by 4 | Viewed by 2433

Abstract

Aloe vera (A. vera) has been studied as a treatment option for ulcerative colitis (UC), but there is a lack of scientific evidence showing whether treatment with Aloe saponaria (A. saponaria) can also be beneficial. To investigate the therapeutic [...] Read more.

Aloe vera (A. vera) has been studied as a treatment option for ulcerative colitis (UC), but there is a lack of scientific evidence showing whether treatment with Aloe saponaria (A. saponaria) can also be beneficial. To investigate the therapeutic potential of A. saponaria as a treatment for UC, clinical symptoms, histopathological characteristics of the colon, inflammatory response, and toxicity were analyzed in dextran sulfate sodium (DSS)-induced UC mice after administration of aqueous extracts of A. saponaria (AAS) for 7 days. The total polyphenol and tannin content of AAS was 272 µg/g and 163 µg/g, respectively. AAS exhibited significant antioxidant activity. Several clinical symptoms, including body weight, colon length, and hematochezia, remarkably improved in the DSS+AAS treated group compared to the DSS+Vehicle-treated group. In addition, similar improvements were detected in the histopathological characteristics and mucin-secreting ability in the colon of DSS-induced UC mice after the administration of AAS. The levels of infiltrated inflammatory cells and cytokine expression were significantly decreased in a dose-dependent manner in the colon of the DSS+AAS-treated group. These alterations in inflammatory response were accompanied by a significant recovery of the protein kinase C/extracellular signal-regulated kinase (PKC/ERK) and phosphatidylinositol-3-kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathways. However, the levels of key markers for hepatotoxicity and nephrotoxicity consistently remained between those of the DSS+AAS-treated and the No groups. Therefore, the results of the present study provide novel evidence that AAS may improve the clinical symptoms and attenuate the inflammatory response in DSS-induced UC mice and does not have any significant hepatotoxicity or nephrotoxicity. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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16 pages, 2238 KiB

Open AccessArticle

Ozoile Reduces the LPS-Induced Inflammatory Response in Colonic Epithelial Cells and THP-1 Monocytes

by Maria Paola Bertuccio, Valentina Rizzo, Salvatore Arena, Alessandra Trainito, Angela Simona Montalto, Daniela Caccamo, Monica Currò, Carmelo Romeo and Pietro Impellizzeri

Curr. Issues Mol. Biol. 2023, 45(2), 1333-1348; https://doi.org/10.3390/cimb45020087 - 5 Feb 2023

Cited by 9 | Viewed by 2681

Abstract

Inappropriate activation of immune functions in intestinal epithelial cells can lead to inflammation that is characterized also by infiltration into intestinal tissue of monocytes/macrophages. Current therapies for intestinal inflammation include anti-inflammatory, immunosuppressive and biological drugs. Ozoile (stable ozonides) has been reported to exert [...] Read more.

Inappropriate activation of immune functions in intestinal epithelial cells can lead to inflammation that is characterized also by infiltration into intestinal tissue of monocytes/macrophages. Current therapies for intestinal inflammation include anti-inflammatory, immunosuppressive and biological drugs. Ozoile (stable ozonides) has been reported to exert anti-inflammatory effects. However, ozonated oil has been used mainly for topical applications and no data are available about its effects on intestinal cells or immune cells. In this study, we evaluated Ozoile effects on human HT-29 colonic cells and THP-1 monocytic cells stimulated with LPS to induce inflammation. HT-29 and THP-1 cells were treated with LPS in the presence/absence of Ozoile for 4 h. Biomarkers of inflammation, some members of tight junctions and the adhesion molecule ICAM were assessed by qRT-PCR. Protein expression was analyzed by Western blotting. The release of TNF-α and IL-1β was measured by ELISA. In HT-29, Ozoile inhibited LPS-induced expression of TNF-α, IL-1β, ZO-1, CLDN1, NOS2 and MMP-2 and increased the expression of Nrf2 and SOD2 antioxidant proteins. In THP-1 cells, the LPS induction of TNF-α, IL-1β and ICAM was counteracted by Ozoile treatment. Our in vitro results demonstrate the effectiveness of Ozoile in reducing the inflammatory response in intestinal and monocytic cells. Further in vivo studies are necessary to confirm its possible use for intestinal inflammatory conditions. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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33 pages, 83157 KiB

Open AccessArticle

Carica Papaya Reduces High Fat Diet and Streptozotocin-Induced Development of Inflammation in Adipocyte via IL-1β/IL-6/TNF-α Mediated Signaling Mechanisms in Type-2 Diabetic Rats

by Jeane Rebecca Roy, Coimbatore Sadagopan Janaki, Selvaraj Jayaraman, Vijayalakshmi Periyasamy, Thotakura Balaji, Madhavan Vijayamalathi, Vishnu Priya Veeraraghavan, Kalaiselvi Krishnamoorthy and Monisha Prasad

Curr. Issues Mol. Biol. 2023, 45(2), 852-884; https://doi.org/10.3390/cimb45020056 - 18 Jan 2023

Cited by 7 | Viewed by 2608

Abstract

The prevalence of obesity in contemporary society has brought attention to how serious it is all around the world. Obesity, a proinflammatory condition defined by hypertrophied adipocytes and immune cells that reside in adipose tissue, is characterized by elevated circulating levels of proinflammatory [...] Read more.

The prevalence of obesity in contemporary society has brought attention to how serious it is all around the world. Obesity, a proinflammatory condition defined by hypertrophied adipocytes and immune cells that reside in adipose tissue, is characterized by elevated circulating levels of proinflammatory cytokines. The pro-inflammatory mediators trigger a number of inflammatory pathways and affect the phosphorylation of a number of insulin-signaling pathways in peripheral tissues. In this work, we pointed the outcome of the leaves of Carica papaya (C. papaya) on the inflammatory molecules by in vivo and in silico analysis in order to prove its mechanisms of action. Adipocytokines, antioxidant enzymes, gene and protein expression of pro-inflammatory signaling molecules (mTOR, TNF-α, IL-1β, IL-6 and IKKβ) by q-RT-PCR and immunohistochemistry, as well as histopathological analysis, in adipose tissues were carried out. C. papaya reinstated the levels of adipocytokines, antioxidant enzymes and mRNA levels of mTOR, TNF-α, IL-1β, IL-6 and IKKβ in the adipose tissues of type 2 diabetic rats. Molecular docking and dynamics simulation studies revealed that caffeic acid, transferulic acid and quercetin had the top hit rates against IKKβ, TNF-α, IL-6, IL-1β, and mTOR. This study concludes that C. papaya put back the altered effects in fatty tissue of type 2 diabetic rats by restoring the adipocytokines and the gene expression. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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9 pages, 1242 KiB

Open AccessArticle

Caffeic Acid Phenethyl Ester Induces Vascular Endothelial Growth Factor Production and Inhibits CXCL10 Production in Human Dental Pulp Cells

by Hitomi Kuramoto, Tadashi Nakanishi, Daisuke Takegawa, Katsuhiro Mieda and Keiichi Hosaka

Curr. Issues Mol. Biol. 2022, 44(11), 5691-5699; https://doi.org/10.3390/cimb44110385 - 15 Nov 2022

Cited by 4 | Viewed by 1881

Abstract

The survival rate of root non-vital teeth is lower than that of vital teeth. Therefore, to preserve the dental pulp is very important. The vascular endothelial growth factor (VEGF) is the most potent angiogenic factor involved in the vitality of dental pulp including [...] Read more.

The survival rate of root non-vital teeth is lower than that of vital teeth. Therefore, to preserve the dental pulp is very important. The vascular endothelial growth factor (VEGF) is the most potent angiogenic factor involved in the vitality of dental pulp including reparative dentin formation. Caffeic acid phenethyl ester (CAPE) is a physiologically active substance of propolis and has some bioactivities such as anti-inflammatory effects. However, there are no reports on the effects of CAPE on dental pulp inflammation. In this study, we investigated the effects of CAPE on VEGF and inflammatory cytokine production in human dental pulp cells (HDPCs) to apply CAPE to an ideal dental pulp protective agent. We found that CAPE induced VEGF production from HDPCs. Moreover, CAPE induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases (ERK), and stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) in HDPCs. Furthermore, CAPE inhibited C-X-C motif chemokine ligand 10 (CXCL10) production in Pam3CSK4- and tumor necrosis factor-alpha (TNF-α)-stimulated HDPCs. In conclusion, these results suggest that CAPE might be useful as a novel biological material for vital pulp therapy by exerting the effects of VEGF production and anti-inflammatory activities. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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11 pages, 2852 KiB

Open AccessArticle

Sargassum horneri (Turner) C. Agardh Extract Regulates Neuroinflammation In Vitro and In Vivo

by Jun Hwi Cho, Dae Hyun Kim, Jong Suk Lee, Mi-Suk Seo, Mi Eun Kim and Jun Sik Lee

Curr. Issues Mol. Biol. 2022, 44(11), 5416-5426; https://doi.org/10.3390/cimb44110367 - 3 Nov 2022

Cited by 7 | Viewed by 2016

Abstract

Previously, we reported that Sargassum horneri (Turner) C. Agardh (S. horneri) is a brown algae species that exerts anti-inflammatory activity toward murine macrophages. However, the anti-neuroinflammatory effects and the mechanism of S. horneri on microglia cells are still unknown. We investigated [...] Read more.

Previously, we reported that Sargassum horneri (Turner) C. Agardh (S. horneri) is a brown algae species that exerts anti-inflammatory activity toward murine macrophages. However, the anti-neuroinflammatory effects and the mechanism of S. horneri on microglia cells are still unknown. We investigated the anti-neuroinflammatory effects of S. horneri extract on microglia in vitro and in vivo. In the present study, we found that S. horneri was not cytotoxic to BV-2 microglia cells and it significantly decreased lipopolysaccharide (LPS)-induced NO production. Moreover, S. horneri also diminished the protein expression of iNOS, COX-2, and cytokine production, including IL-1β, TNF-α, and IL-6, on LPS-stimulated microglia activation. S. horneri elicited anti-neuroinflammatory effects by inhibiting phosphorylation of p38 MAPK and NF-κB. In addition, S. horneri inhibited astrocytes and microglia activation in LPS-challenged mice brain. Therefore, these results suggested that S. horneri exerted anti-neuroinflammatory effects on LPS-stimulated microglia cell activation by inhibiting neuroinflammatory factors and NF-κB signaling. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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15 pages, 4147 KiB

Open AccessArticle

Cardamom Extract Alleviates the Oxidative Stress, Inflammation and Apoptosis Induced during Acetaminophen-Induced Hepatic Toxicity via Modulating Nrf2/HO-1/NQO-1 Pathway

by Essraa A. R. Alkhalifah, Amjad A. Alobaid, Marwah A. Almajed, Manar K. Alomair, Lama S. Alabduladheem, Sarah F. Al-Subaie, Abdullah Akbar, Mahesh V. Attimarad, Nancy S. Younis and Maged E. Mohamed

Curr. Issues Mol. Biol. 2022, 44(11), 5390-5404; https://doi.org/10.3390/cimb44110365 - 2 Nov 2022

Cited by 10 | Viewed by 2417

Abstract

Acetaminophen (APAP) is the most extensively used and safest analgesic and antipyretic drug worldwide; however, its toxicity is associated with life-threatening acute liver failure. Cardamom (CARD), a sweet, aromatic, commonly used spice, has several pharmacological actions. In the current study, we tried to [...] Read more.

Acetaminophen (APAP) is the most extensively used and safest analgesic and antipyretic drug worldwide; however, its toxicity is associated with life-threatening acute liver failure. Cardamom (CARD), a sweet, aromatic, commonly used spice, has several pharmacological actions. In the current study, we tried to explore the chemical composition and the hepato-protective effect of ethanolic aqueous extract of CARD to mitigate APAP-induced hepatic toxicity and elucidate its underlying mechanism of action. Material and methods: Aqueous CARD extract was subjected to LC-TOF-MS analysis to separate and elucidate some of its components. In vivo animal experiments involved five groups of animals. In the normal and cardamom groups, mice were administered either saline or CARD (200 mg/kg), respectively, orally daily for 16 days. In the APAP group, the animals were administered saline orally daily for 15 days, and on the 16th day, animals were administered APAP (300 mg/kg) IP for the induction of acute hepatic failure. In the CARD 200 + APAP group, mice were administered CARD (200 mg/kg) for 15 days, followed by APAP on the 16th day. Results: The aqueous extract of CARD showed several compounds, belonging to polyphenol, flavonoids, cinnamic acid derivatives and essential oil components. In the in vivo investigations, APAP-induced impaired liver function, several histopathological alterations, oxidative stress and inflammatory and apoptotic status signified severe hepatic failure. Whereas, pretreatment with the CARD extract prior to APAP administration diminished serum levels of the hepatic function test and augmented Nrf2 nucleoprotein and HO-1 and NQO-1. CARD down-regulated MDA, inflammatory mediators (IL-1β, IL-6, TNF-α and NF-κB) and apoptotic markers (caspase 3 and 9 and Bax) and amplified the activities of SOD, catalase, GSH-Px and GSH-R in hepatic tissue samples. Conclusion: CARD extract mitigated the hepatic toxicity induced by APAP. The underlying mechanism of action of such hepato-protective action may be through upregulation of the Nrf2/HO-1/NQO-1 pathway with subsequent alleviation of the oxidative stress, inflammation and apoptosis induced by APAP. Many of the compounds identified in the CARD extract could be attributed to this pharmacological action of the extract. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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12 pages, 2164 KiB

Open AccessArticle

Western Diet-Fed ApoE Knockout Male Mice as an Experimental Model of Non-Alcoholic Steatohepatitis

by Felipe N. Camargo, Sandro L. Matos, Layanne C. C. Araujo, Carla R. O. Carvalho, Andressa G. Amaral and João Paulo Camporez

Curr. Issues Mol. Biol. 2022, 44(10), 4692-4703; https://doi.org/10.3390/cimb44100320 - 8 Oct 2022

Cited by 15 | Viewed by 3936

Abstract

One of the consequences of the Western lifestyle and high-fat diet is non-alcoholic fatty liver disease (NAFLD) and its aggressive form, non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma (HCC) and is rapidly becoming the leading cause of end-stage liver [...] Read more.

One of the consequences of the Western lifestyle and high-fat diet is non-alcoholic fatty liver disease (NAFLD) and its aggressive form, non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma (HCC) and is rapidly becoming the leading cause of end-stage liver disease or liver transplantation. Currently, rodent NASH models lack significant aspects of the full NASH spectrum, representing a major problem for NASH research. Therefore, this work aimed to characterize a fast rodent model with all characteristic features of NASH. Eight-week-old male ApoE KO mice were fed with Western diet (WD), high fatty diet (HFD) or normal chow (Chow) for 7 weeks. Whole-body fat was increased by ~2 times in WD mice and HFD mice and was associated with increased glucose intolerance, hepatic triglycerides, and plasma ALT and plasma AST compared with Chow mice. WD mice also showed increased galectin-3 expression compared with Chow or HFD mice and increased plasma cholesterol compared with Chow mice. WD and HFD displayed increased hepatic fibrosis and increased F4/80 expression. WD mice also displayed increased levels of plasma MCP-1. Hepatic inflammatory markers were evaluated, and WD mice showed increased levels of TNF-α, MCP-1, IL-6 and IFN-γ. Taken together, these data demonstrated that the ApoE KO mouse fed with WD is a great model for NASH research, once it presents the fundamental parameters of the disease, including hepatic steatosis, fibrosis, inflammation, and metabolic syndrome. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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10 pages, 1444 KiB

Open AccessArticle

Suppressive Effects of 4-(Phenylsulfanyl) Butan-2-One on CCL-1 Production via Histone Acetylation in Monocytes

by Ming-Kai Tsai, Mei-Lan Tsai, Zhi-Hong Wen, Wei-Ting Liao, Yi-Ching Lin, Hsin-Ying Clair Chiou, Ming-Hong Lin and Chih-Hsing Hung

Curr. Issues Mol. Biol. 2022, 44(10), 4616-4625; https://doi.org/10.3390/cimb44100315 - 3 Oct 2022

Cited by 2 | Viewed by 1741

Abstract

The 4-(phenylsulfanyl) butan-2-one (4-PSB-2), a marine-derived compound from soft coral, was proven to have multiple biological activities including neuroprotection and potent anti-inflammatory effects. CC chemokine ligand (CCL)-1 belongs to T helper (Th)2-related chemokines that are involved in the recruitment of Th2 inflammatory cells. [...] Read more.

The 4-(phenylsulfanyl) butan-2-one (4-PSB-2), a marine-derived compound from soft coral, was proven to have multiple biological activities including neuroprotection and potent anti-inflammatory effects. CC chemokine ligand (CCL)-1 belongs to T helper (Th)2-related chemokines that are involved in the recruitment of Th2 inflammatory cells. Histone acetylation has been recognized as a critical mechanism underlying the regulated cytokine and chemokine production. Our study tried to investigate the anti-inflammatory effect of 4-PSB-2 on CCL-1 production in human monocytes and explore possible underlying intracellular processes, including epigenetic regulation. To confirm our hypothesis, human monocyte THP-1 cell line and primary CD14⁺ cells were pretreated with various concentrations of 4-PSB-2 and then were stimulated with lipopolysaccharide (LPS). The CCL-1 concentration was measured by enzyme-linked immunosorbent assays, and the intracellular signaling pathways and epigenetic regulation of 4-PSB-2 were investigated by using Western blotting and chromatin immunoprecipitation analysis. In this study, we found that 4-PSB-2 had a suppressive effect on LPS-induced CCL-1 production. Moreover, this suppressive effect of 4-PSB-2 was mediated via intracellular signaling such as the mitogen-activated protein kinase and nuclear factor-κB pathways. In addition, 4-PSB-2 could suppress CCL-1 production by epigenetic regulation through downregulating histone H3 and H4 acetylation. In short, our study demonstrated that 4-PSB-2 may have a potential role in the treatment of allergic inflammation. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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15 pages, 3380 KiB

Open AccessArticle

A New EGFR Inhibitor from Ficus benghalensis Exerted Potential Anti-Inflammatory Activity via Akt/PI3K Pathway Inhibition

by Rania Alaaeldin, Heba Ali Hassan, Islam M. Abdel-Rahman, Reham H. Mohyeldin, Nancy Youssef, Ahmed E. Allam, Sayed F. Abdelwahab, Qing-Li Zhao and Moustafa Fathy

Curr. Issues Mol. Biol. 2022, 44(7), 2967-2981; https://doi.org/10.3390/cimb44070205 - 2 Jul 2022

Cited by 21 | Viewed by 3219

Abstract

Inflammation is a critical defensive mechanism mainly arising due to the production of prostaglandins via cyclooxygenase enzymes. This study aimed to examine the anti-inflammatory activity of fatty acid glucoside (FAG), which is isolated from Ficus benghalensis against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The [...] Read more.

Inflammation is a critical defensive mechanism mainly arising due to the production of prostaglandins via cyclooxygenase enzymes. This study aimed to examine the anti-inflammatory activity of fatty acid glucoside (FAG), which is isolated from Ficus benghalensis against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The cytotoxic activity of the FAG on RAW 264.7 macrophages was evaluated with an MTT assay. The levels of PGE2 and NO and the activity of iNOS, COX-1, and COX-2 enzymes in LPS-stimulated RAW 264.7 cells were evaluated. The gene expression of IL-6, TNF-α, and PGE2 was investigated by qRT-PCR. The expression of epidermal growth factor receptor (EGFR), Akt, and PI3K proteins was examined using Western blotting analysis. Furthermore, molecular docking of the new FAG against EGFR was investigated. A non-cytotoxic concentration of FAG increased NO release and iNOS activity, inhibited COX-1 and COX-2 activities, and reduced PGE2 levels in LPS-stimulated RAW 264.7 cells. It diminished the expression of TNF-α, IL-6, PGE2, EGFR, Akt, and PI3K. Furthermore, the molecular docking study proposed the potential direct binding of FAG with EGFR with a high affinity. This study showed that FAG is a natural EGFR inhibitor, NO-releasing, and COX-inhibiting anti-inflammatory agent via EGFR/Akt/PI3K pathway inhibition. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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8 pages, 1483 KiB

Open AccessArticle

6-(Methylsulfinyl) Hexyl Isothiocyanate Inhibits IL-6 and CXCL10 Production in TNF-α-Stimulated Human Oral Epithelial Cells

by Masahiro Shimoyama, Yoshitaka Hosokawa, Ikuko Hosokawa, Kazumi Ozaki and Keiichi Hosaka

Curr. Issues Mol. Biol. 2022, 44(7), 2915-2922; https://doi.org/10.3390/cimb44070201 - 29 Jun 2022

Cited by 6 | Viewed by 2381

Abstract

6-(Methylsulfinyl) hexyl isothiocyanate (6-MSITC) is a bioactive substance found in wasabi (Wasabia japonica) and has been reported to have some bioactive effects including anticancer and antioxidant effects. However, there are no reports on its effects on periodontal resident cells, and many points remain [...] Read more.

6-(Methylsulfinyl) hexyl isothiocyanate (6-MSITC) is a bioactive substance found in wasabi (Wasabia japonica) and has been reported to have some bioactive effects including anticancer and antioxidant effects. However, there are no reports on its effects on periodontal resident cells, and many points remain unclear. In this study, we aimed to investigate whether 6-MSITC exerts anti-inflammatory effects on human oral epithelial cells, including effects on signal transduction pathway activation. 6-MSITC inhibited interleukin (IL)-6 and C-X-C motif chemokine ligand 10 (CXCL10) production in TNF-α-stimulated TR146 cells, which are a human oral epithelial cell line. Moreover, we found that 6-MSITC could suppress signal transducer and activator of transcription (STAT)3, nuclear factor (NF)-κB, and p70S6 kinase (p70S6K)-S6 ribosomal protein (S6) pathways activation in TNF-α-stimulated TR146 cells. Furthermore, STAT3 and NF-κB inhibitors could suppress IL-6 and CXCL10 production in TNF-α-treated TR146 cells. In summary, 6-MSITC could decrease IL-6 and CXCL10 production in human oral epithelial cell by inhibiting STAT3 and NF-κB activation. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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11 pages, 3967 KiB

Open AccessArticle

Apigetrin Abrogates Lipopolysaccharide-Induced Inflammation in L6 Skeletal Muscle Cells through NF-κB/MAPK Signaling Pathways

by Sang-Eun Ha, Pritam Bhagwan Bhosale, Hun-Hwan Kim, Min-Yeong Park, Abuyaseer Abusaliya, Gon-Sup Kim and Jin-A Kim

Curr. Issues Mol. Biol. 2022, 44(6), 2635-2645; https://doi.org/10.3390/cimb44060180 - 8 Jun 2022

Cited by 8 | Viewed by 2412

Abstract

Apigetrin is a glycosidic flavonoid derived from Teucrium gnaphalodes that has a wide range of biological activities, including antioxidant, anti-inflammatory, and anticancer. Inflammation is a kind of defense mechanism in the body. Flavonoids are natural phytochemicals that exert anti-inflammatory effects in numerous cells. [...] Read more.

Apigetrin is a glycosidic flavonoid derived from Teucrium gnaphalodes that has a wide range of biological activities, including antioxidant, anti-inflammatory, and anticancer. Inflammation is a kind of defense mechanism in the body. Flavonoids are natural phytochemicals that exert anti-inflammatory effects in numerous cells. In the present study, we investigated the anti-inflammatory effect of apigetrin and its underlying mechanism of activity in skeletal muscle cells (L6). The determination of cytotoxicity was performed by MTT assay. We treated L6 cells with apigetrin, and nontoxic concentrations were chosen to perform further experimentation. Apigetrin inhibited the expression of iNOS and COX-2 induced by LPS in a dose-dependent manner. iNOS and COX-2 are inflammatory markers responsible for enhancing the inflammatory response. Apigetrin also inhibited the LPS-induced phosphorylation of p65 and IκB-α. NF-κB signaling regulates the inflammatory process by mediating various proinflammatory genes. Similarly, the MAPK signaling pathway consists of ERK, JNK, and p38, which plays a critical role in the production of cytokines and downstream signaling events leading to inflammation. Apigetrin significantly downregulated the phosphorylation of JNK and p38, but did not affect the phosphorylation of ERK in the LPS-stimulated cells. These findings indicate the correlation between the anti-inflammatory activity of NF-κB and the MAPK signaling pathway. Thus, our overall finding suggests that apigetrin has anti-inflammatory effects and it can be considered for further drug design on L6 skeletal muscle cells. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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Review

Jump to: Editorial, Research

16 pages, 544 KiB

Open AccessReview

The Integral Role of Diets Including Natural Products to Manage Rheumatoid Arthritis: A Narrative Review

by Ayse Gunes-Bayir, Beyza Mendes and Agnes Dadak

Curr. Issues Mol. Biol. 2023, 45(7), 5373-5388; https://doi.org/10.3390/cimb45070341 - 28 Jun 2023

Cited by 6 | Viewed by 3720

Abstract

Genetic and environmental factors including lifestyle are thought to play a key role in the pathophysiology of rheumatoid arthritis (RA). There is evidence that diet can enhance the inflammatory response in genetically predisposed individuals. On the other hand, certain types of diets can [...] Read more.

Genetic and environmental factors including lifestyle are thought to play a key role in the pathophysiology of rheumatoid arthritis (RA). There is evidence that diet can enhance the inflammatory response in genetically predisposed individuals. On the other hand, certain types of diets can alleviate RA symptoms due to their anti-inflammatory and antioxidant activities. Also, natural compounds with potential effectiveness in RA management belong to different chemical classes such as flavonoids, polyphenols, carotenoids, and alkaloids with their antioxidant characteristics as well as probiotics. The nutritional approaches to prevent or extenuate the disease progress were examined in this narrative review which was conducted using the PubMed, ScienceDirect and Google Scholar databases and conforms to the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines. Mediterranean and vegan diets equally have been shown to exhibit positive effects on RA as the consumption of dietary fiber, antioxidants and anti-inflammatory compounds from fruits, vegetables, grains, nuts, and seeds are high. Whereas Mediterranean diet additionally includes beneficial nutrients of animal origin such as omega-3 polyunsaturated fatty acids from fish and seafood, patients on vegan diet need to be monitored closely for intake of all critical nutrients. Certain calorie restrictions and intermittent fasting diets have been shown to benefit RA patients although there is an obvious need for further studies to establish solid evidence-based recommendations and guidelines. The research data available strongly suggest that dietary approaches with anti-inflammatory properties may help delay the onset of RA and/or improve symptoms and thus nutrition should be routinely addressed to facilitate management of the disease. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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27 pages, 2186 KiB

Open AccessReview

Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?

by Eleonora A. Starikova, Artem A. Rubinstein, Jennet T. Mammedova, Dmitry V. Isakov and Igor V. Kudryavtsev

Curr. Issues Mol. Biol. 2023, 45(4), 3525-3551; https://doi.org/10.3390/cimb45040231 - 18 Apr 2023

Cited by 10 | Viewed by 2856

Abstract

More than a century has passed since arginine was discovered, but the metabolism of the amino acid never ceases to amaze researchers. Being a conditionally essential amino acid, arginine performs many important homeostatic functions in the body; it is involved in the regulation [...] Read more.

More than a century has passed since arginine was discovered, but the metabolism of the amino acid never ceases to amaze researchers. Being a conditionally essential amino acid, arginine performs many important homeostatic functions in the body; it is involved in the regulation of the cardiovascular system and regeneration processes. In recent years, more and more facts have been accumulating that demonstrate a close relationship between arginine metabolic pathways and immune responses. This opens new opportunities for the development of original ways to treat diseases associated with suppressed or increased activity of the immune system. In this review, we analyze the literature describing the role of arginine metabolism in the immunopathogenesis of a wide range of diseases, and discuss arginine-dependent processes as a possible target for therapeutic approaches. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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19 pages, 2144 KiB

Open AccessReview

Effect of Nigella sativa on Selected Gastrointestinal Diseases

by Sara Jarmakiewicz-Czaja, Magdalena Zielińska, Kacper Helma, Aneta Sokal and Rafał Filip

Curr. Issues Mol. Biol. 2023, 45(4), 3016-3034; https://doi.org/10.3390/cimb45040198 - 3 Apr 2023

Cited by 9 | Viewed by 6363

Abstract

Nigella sativa L. (family Ranunculaceae), also known as black cumin, has been used in cuisine around the world for many years. Due to its health-promoting properties, it can be used not only in the food industry but also in medicine. The main [...] Read more.

Nigella sativa L. (family Ranunculaceae), also known as black cumin, has been used in cuisine around the world for many years. Due to its health-promoting properties, it can be used not only in the food industry but also in medicine. The main bioactive compound contained in the black cumin extract is thymoquinone (TQ), which has a special therapeutic role. The results of research in recent years confirmed its hypoglycemic, hypolipemic, and hepatoprotective effects, among others. In addition, the results of laboratory tests also indicate its immunomodulatory and anticancer effects, although there is still a lack of data on the mechanisms of how they are involved in the fight against cancer. Including this plant material in one’s diet can be both an element of prophylaxis and therapy supporting the treatment process, including pharmacological treatment. However, attention should be paid to its potential interactions with drugs used in the treatment of chronic diseases. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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14 pages, 1311 KiB

Open AccessReview

Garlic (Allium sativum L.) as an Ally in the Treatment of Inflammatory Bowel Diseases

by Silvana Zugaro, Elisabetta Benedetti and Giulia Caioni

Curr. Issues Mol. Biol. 2023, 45(1), 685-698; https://doi.org/10.3390/cimb45010046 - 11 Jan 2023

Cited by 16 | Viewed by 9147

Abstract

For centuries, garlic (Allium sativum) has been used both as a traditional remedy for most health-related ailments and for culinary purposes. Current preclinical investigations have suggested that dietary garlic intake has beneficial health effects, such as antioxidant, anti-inflammatory, antitumor, antiobesity, antidiabetic, [...] Read more.

For centuries, garlic (Allium sativum) has been used both as a traditional remedy for most health-related ailments and for culinary purposes. Current preclinical investigations have suggested that dietary garlic intake has beneficial health effects, such as antioxidant, anti-inflammatory, antitumor, antiobesity, antidiabetic, antiallergic, cardioprotective, and hepatoprotective effects. Its therapeutic potential is influenced by the methods of use, preparation, and extraction. Of particular importance is the Aged Garlic Extract (AGE). During the aging process, the odorous, sour, and irritating compounds in fresh raw garlic, such as allicin, are naturally converted into stable and safe compounds that have significantly greater therapeutic effects than fresh garlic. In AGE, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC) are the major water-soluble organosulfurized compounds (OSCs). SAC has been extensively studied, demonstrating remarkable antioxidant, anti-inflammatory, and immunomodulatory capacities. Recently, AGE has been suggested as a promising candidate for the maintenance of immune system homeostasis through modulation of cytokine secretion, promotion of phagocytosis, and activation of macrophages. Since immune dysfunction plays an important role in the development and progress of various diseases, given the therapeutic effects of AGE, it can be thought of exploiting its immunoregulatory capacity to contribute to the treatment and prevention of chronic inflammatory bowel diseases (IBD). Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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10 pages, 629 KiB

Open AccessReview

Non-Peptide Agonists and Antagonists of the Prokineticin Receptors

by Roberta Lattanzi and Rossella Miele

Curr. Issues Mol. Biol. 2022, 44(12), 6323-6332; https://doi.org/10.3390/cimb44120431 - 12 Dec 2022

Cited by 11 | Viewed by 2167

Abstract

The prokineticin family comprises a group of secreted peptides that can be classified as chemokines based on their structural features and chemotactic and immunomodulatory functions. Prokineticins (PKs) bind with high affinity to two G protein-coupled receptors (GPCRs). Prokineticin receptor 1 (PKR1) and prokineticin [...] Read more.

The prokineticin family comprises a group of secreted peptides that can be classified as chemokines based on their structural features and chemotactic and immunomodulatory functions. Prokineticins (PKs) bind with high affinity to two G protein-coupled receptors (GPCRs). Prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2) are involved in a variety of physiological functions such as angiogenesis and neurogenesis, hematopoiesis, the control of hypothalamic hormone secretion, the regulation of circadian rhythm and the modulation of complex behaviors such as feeding and drinking. Dysregulation of the system leads to an inflammatory process that is the substrate for many pathological conditions such as cancer, pain, neuroinflammation and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The use of PKR’s antagonists reduces PK2/PKRs upregulation triggered by various inflammatory processes, suggesting that a pharmacological blockade of PKRs may be a successful strategy to treat inflammatory/neuroinflammatory diseases, at least in rodents. Under certain circumstances, the PK system exhibits protective/neuroprotective effects, so PKR agonists have also been developed to modulate the prokineticin system. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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18 pages, 830 KiB

Open AccessReview

Anti-Inflammatory and Hypouricemic Effect of Bioactive Compounds: Molecular Evidence and Potential Application in the Management of Gout

by Anna Scanu, Roberto Luisetto, Roberta Ramonda, Paolo Spinella, Paolo Sfriso, Paola Galozzi and Francesca Oliviero

Curr. Issues Mol. Biol. 2022, 44(11), 5173-5190; https://doi.org/10.3390/cimb44110352 - 25 Oct 2022

Cited by 11 | Viewed by 4740

Abstract

Gout is caused by the deposition of monosodium urate crystals in the joint and represents the most common form of inflammatory arthritis in men. Its prevalence is rising worldwide mainly due to the increase of risk factors associated with the disease, in particular [...] Read more.

Gout is caused by the deposition of monosodium urate crystals in the joint and represents the most common form of inflammatory arthritis in men. Its prevalence is rising worldwide mainly due to the increase of risk factors associated with the disease, in particular hyperuricemia. Besides gout, hyperuricemia leads to an increased inflammatory state of the body with consequent increased risk of comorbidities such as cardiovascular diseases. Increasing evidence shows that bioactive compounds have a significant role in fighting inflammatory and immune chronic conditions. In gout and hyperuricemia, these molecules can exert their effects at two levels. They can either decrease serum uric acid concentrations or fight inflammation associated with monosodium urate crystals deposits and hyperuricemia. In this view, they might be considered valuable support to the pharmacological therapy and prevention of the disease. This review aims to provide an overview of the beneficial role of bioactive compounds in hyperuricemia, gout development, and inflammatory pathways of the disease. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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14 pages, 590 KiB

Open AccessReview

Anti-Inflammatory Activity of Bilberry (Vaccinium myrtillus L.)

by Anshul Sharma and Hae-Jeung Lee

Curr. Issues Mol. Biol. 2022, 44(10), 4570-4583; https://doi.org/10.3390/cimb44100313 - 30 Sep 2022

Cited by 23 | Viewed by 3643

Abstract

Inflammation is important in the pathogenesis of several chronic diseases. The anti-inflammatory properties of berries have been investigated but the anti-inflammatory activity of bilberry has received little attention and a detailed review is yet to be published. Therefore, we compiled information on the [...] Read more.

Inflammation is important in the pathogenesis of several chronic diseases. The anti-inflammatory properties of berries have been investigated but the anti-inflammatory activity of bilberry has received little attention and a detailed review is yet to be published. Therefore, we compiled information on the phytochemicals of bilberry and preclinical and clinical studies of its anti-inflammatory properties. The review was based on studies from 2007 to date. Phytoconstituents of bilberries were phenolic acids, organic acids, anthocyanins, coumarins, flavonols, flavanols, tannins, terpenoids, and volatile chemicals. Data from cell and animal model studies show that bilberry has an anti-inflammatory effect by lowering tumor necrosis factor-α, interleukin (IL)-6, and IL-1β expression, inducing nitric oxide synthases and cyclooxygenases, and altering the nuclear factor kappa B and Janus kinase-signal transducer and activator of transcription signaling pathways. Bilberry supplementation as fruits (frozen, processed, and whole), juices, and anthocyanins reduced levels of inflammatory markers in most clinical studies of metabolic disorders. Therefore, bilberry may be useful for the prevention and treatment of chronic inflammatory disorders. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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